DESCRIPTION (adapted from the application): The long term objective of this project is to develop methods for gene therapy of cystic fibrosis (CF). The project has two specific aims. The first aim is to identify the cells that express the cystic fibrosis transmembrane conductance regulator (CFTR) in the lung. This will be done by using monoclonal antibodies to CFTR. The second specific aim is to develop the molecular tools that are needed to deliver and stably express genes in those cells. The tissue specific expression of the polymeric immunoglobulin receptor (pIgR) will be used to target non-degradative internalization of macromolecules from the basolateral surface. A Fab fragment of antibody to pIgR covalently coupled to a polycation link to DNA will be used to direct foreign DNA into the desired cells. The specificity of the targeting will be determined and uptake and expression of the DNA optimized.